The proposed studies are aimed toward an understanding of the genetics and the regulatory mechanisms controlling the immunoglobulin VH region. Specifically, colonies of homozygous suppressed auto-immunized (to the a plus allotypes) rabbits will be established as a ready source of immunoglobulin bearing the VH a minus allotypes. Specific antisera to the various a minus allotypes and the unique determinants will be produced to facilitate biochemical and serological comparative analysis with a plus Ig and Ig from other lagomorph species. Multiple VH allotype suppression should further coax the VH region into expressing minor and silent VH allotypes. Suppressed and hyperimmunized suppressed rabbits will be assayed for latent allotypes in an attempt to establish a genetic mechanism for their expression. Clues to the functional and evolutionary significance of the a minus allotypes and the unique determinants may be obtained by testing the ability of B cells expressing these determinants to generate an immune response. Thus, insights into the mechanism of the generation of diversity may be revealed. The mechanism of allotype dominance by a plus Ig will be investigated by analysis of the ontogeny of a plus and a minus B cells, while mixed rosetting of B cells will be used to probe the possibility of allelic (subgroup; e.g, a plus and a minus) inclusion.